Cesium carbonate → 4'-Fluoro-1'-{[3-(trifluoromethyl)pyridin-2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'h)-one

HRID 2385306Notes

Reaction equation

HRID 2385306 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]1([C:23]3[C:14](=[CH:15][C:16]4[O:21][CH2:20][CH2:19][O:18][C:17]=4[CH:22]=3)[O:13][CH2:12]1)[C:5](=[O:11])[NH:6]2.Cl.Cl[CH2:26][C:27]1[C:32]([C:33]([F:36])([F:35])[F:34])=[CH:31][CH:30]=[CH:29][N:28]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]1([C:23]3[C:14](=[CH:15][C:16]4[O:21][CH2:20][CH2:19][O:18][C:17]=4[CH:22]=3)[O:13][CH2:12]1)[C:5](=[O:11])[N:6]2[CH2:26][C:27]1[C:32]([C:33]([F:35])([F:34])[F:36])=[CH:31][CH:30]=[CH:29][N:28]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 593524954'-fluoro-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-oneHCID 667065662-(Chloromethyl)-3-(trifluoromethyl)pyridine hydrochloride

Product 1

HCID 593525774'-Fluoro-1'-{[3-(trifluoromethyl)pyridin-2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'h)-oneYield 82.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 4′-fluoro-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.31 g, 1.00 mmol), 2-(chloromethyl)-3-(trifluoromethyl)pyridine hydrochloride (0.29 g, 1.50 mmol) and cesium carbonate (0.98 g, 3.00 mmol) in N,N′ dimethylformamide (10 mL) was heated at 60° C. for 2 h and was filtered while hot. The filtrate was allowed to cool to ambient temperature and water was added, causing a precipitate to be deposited. The solid was collected by filtration, washed with water (50 mL) and dried under vacuum. The residue was recrystallized from N,N′ dimethylformamide/water to afford 4′-fluoro-1′-{[3-(trifluoromethyl)pyridin-2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.39 g, 82%) as a beige solid: mp 245-247° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.68 (d, J=4.5 Hz, 1H), 8.27 (d, J=7.65 Hz, 1H), 7.59 (dd, J=7.8, 4.9 Hz, 1H), 7.30 (ddd, J=8.2, 8.2, 5.8 Hz, 1H), 6.86 (d, J=9.0 Hz, 1H), 6.82 (d, J=7.8 Hz, 1H), 6.54 (s, 1H), 6.49 (s, 1H), 5.25 (ABq, J=17.4 Hz, 2H), 4.79 (q, J=9.4 Hz, 2H), 4.22-4.10 (m, 4H); 13C NMR (75 MHz, DMSO-d6) δ 176.5, 157.9 (d, 1JC-F=247 Hz), 154.6, 152.3, 152.1 (d, 5JC-F=1.2 Hz), 144.9 (d, 4JC-F=8.9 Hz), 144.3, 137.6, 135.1 (q, 4JC-F=4.9 Hz), 130.8 (d, 4JC-F=8.6 Hz), 125.6 (q, 1JC-F=274 Hz), 123.0, 122.9 (d, 2JC-F=32.3 Hz), 119.4, 117.1 (d, 3JC-F=19.3 Hz), 111.5, 109.9 (d, 3JC-F=19.9 Hz), 105.7 (d, 5JC-F=2.9 Hz), 98.4, 77.4, 64.1, 63.5, 56.0 (d, 5JC-F=1.7 Hz), 42.3 (q, 5JC-F=3.3 Hz); MS (ES+) m/z 460.9 (M+1).

Workup

  1. filtrationwas filtered while hot
  2. temperatureto cool to ambient temperature
  3. additionwater was added
  4. filtrationThe solid was collected by filtration
  5. washwashed with water (50 mL)
  6. customdried under vacuum
  7. customThe residue was recrystallized from N,N′ dimethylformamide/water

Sources & evidence

ORD record
ord-2c94af97359344d99b2f25afa88805df
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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